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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2,4 xylenol
- Physical state: Liquid (yellowish)
- Analytical purity: 99.5% (99.5g/100g)
- Impurities (identity and concentrations): Not stated
- Purity test date:Not stated
- Lot/batch No. 14822 JF
- Stability under test conditions: Not stated
- Storage condition of test material: Room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Lutrol E 400 DAB
Concentration / amount:
Intradermal inducton: 0.5% test substance in Lutrol E 400 DAB
Percutaneous induction: 25% test substance in Lutrol E 400 DAB
1st and 2nd Challenge: 5% Test substance in Lutrol E 400 DAB
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Lutrol E 400 DAB
Concentration / amount:
Intradermal inducton: 0.5% test substance in Lutrol E 400 DAB
Percutaneous induction: 25% test substance in Lutrol E 400 DAB
1st and 2nd Challenge: 5% Test substance in Lutrol E 400 DAB
No. of animals per dose:
20 animals/test group
10 animals/control group - 2 control groups

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
other: 1st and 2nd control groups
Dose level:
Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: 1st and 2nd control groups
Dose level:
Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
other: 1st and 2nd control groups
Dose level:
Test substance 5% in Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: 1st control group
Dose level:
Test substance 5% in Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Test substance 5% in Lutrol E 400 DAB
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
discrete or patchy eythema; moderate and confluent erythema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Test substance 5% in Lutrol E 400 DAB. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: discrete or patchy eythema; moderate and confluent erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Test substance 5% in Lutrol E 400 DAB
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
discrete or patchy erythem; moderate and confluent erythema
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Test substance 5% in Lutrol E 400 DAB. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: discrete or patchy erythem; moderate and confluent erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Lutrol E 400 DAB. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Lutrol E 400 DAB. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
other: 1st and 2nd control groups
Dose level:
Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group:
Reading:
rechallenge
Hours after challenge:
48
Group:
other: 1st and 2nd control groups
Dose level:
Test substance 5% in Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group:
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
Test substance 5% in Lutrol E 400 DAB
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
discrete or patchy erythema; moderate and confluent erythema
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: Test substance 5% in Lutrol E 400 DAB. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: discrete or patchy erythema; moderate and confluent erythema.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
Test substance 5% in Lutrol E 400 DAB
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: Test substance 5% in Lutrol E 400 DAB. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: discrete or patchy erythema.
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: Lutrol E 400 DAB. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
Lutrol E 400 DAB
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: Lutrol E 400 DAB. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Results:

Intradermal induction, moderate and copnfluent erythema and swelling were observed at the injection sites of all control group animals and all test group animals at which only Freund's adjuvant in NaCl was applied. Necrotic changes and swelling were observed in the other sites (lutrol E 400 DAB and 50% Lutrol with FCA / 0.9% NaCl(aq)).

Injections with 0.5% test substance in Lutrol E 400 DAB also caused swelling and necrotic skin changes. Moderate and confluent erythema and swelling were observed at the injection sites of all test group animals which were applied with a 0.5% test test substance preparation in FCA/0.9% NaCl (aq).

Percutaneous induction (1 week later): Controls treated with Lutrol E 400 (no reaction). Induction with 2,4 xylenol (25% in Lutrol E 400 DAB) gave rise to swelling and necrotic skin changes.

1st challenge (14 days later): No findings in all control animals at 24 or 48hrs.

Test animals 24hrs: 1/20 intense erythema and swelling; 8/20 moderate and confluent erythema; 2/20 discrete or patchy erythema.

Test animals 48hrs: 4/20 moderate and confluent erythema; 3/20 discrete or patchy erythema.2/20 dscrete or patchy erythema as well as scaling

2nd challenge (1 week later): No findings in all control animals at 24 or 48hrs.

Test animals 24hrs: 4/20 moderate and confluent erythema; 3/20 discrete or patchy erythema.

Test animals 48hrs: 1/20 moderate and confluent erythema; 5/20 discrete or patchy erythema

Challenge and rechallenge results presented above.

Table 1: 1st Control group - intradermal induction:

Form of application

A. Freund’s adjuvant / 0.9% NaCl (aq) 1:1

B Lutrol E 400 DAB

C 50% preparation of Lutrol E 400 DAB with Freund’s adjuvant / 0.9% NaCl (aq) 1:1

Animal

11

12

13

14

15

16

17

18

19

20

24hr

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

 

A

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

B

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

C

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

Table 2: 2nd Control group - intradermal indcution:

Form of application

A. Freund’s adjuvant / 0.9% NaCl (aq) 1:1

B Lutrol E 400 DAB

C 50% preparation of Lutrol E 400 DAB with Freund’s adjuvant / 0.9% NaCl (aq) 1:1

Animal

21

22

23

24

25

26

27

28

29

30

24hr

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

 

A

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

B

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

C

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

 

Table 3: Test group - intradermal induction:

Form of application

A. Freund’s adjuvant / 0.9% NaCl (aq) 1:1

B Test substance 0.5% in Lutrol E 400 DAB

C Test substance 0.5% in Freund’s adjuvant / 0.9% NaCl (aq) 1:1

Animal

31

32

33

34

35

36

37

38

39

40

24hr

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

 

A

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

B

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

C

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

Form of application

A. Freund’s adjuvant / 0.9% NaCl (aq) 1:1

B Test substance 0.5% in Lutrol E 400 DAB

C Test substance 0.5% in Freund’s adjuvant / 0.9% NaCl (aq) 1:1

Animal

41

42

43

44

45

46

47

48

49

50

24hr

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

R

L

 

A

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

B

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

C

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

2E

R = right

L = left

2 = Moderate and confluent erythema

E = swelling

N = necrotic skin changes

Table 4: 1st Control group - percutaneous induction

Form of application: Lutrol E 400 DAB

 

Animal

11

12

13

14

15

16

17

18

19

20

48hr

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

 

Table 5: 2nd Control group - percutaneous induction

Form of application: Lutrol E 400 DAB

 

Animal

21

22

23

24

25

26

27

28

29

30

48hr

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

Table 6: Test group - percutaneous induction

Form of application: Test substance 25% in Lutrol E 400 DAB

 

Animal

31

32

33

34

35

36

37

38

39

40

48hr

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

Form of application: Test substance 25% in Lutrol E 400 DAB

 

Animal

41

42

43

44

45

46

47

48

49

50

48hr

NE

NE

NE

NE

NE

NE

NE

NE

NE

NE

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
A clear sensitising effect was observed for 2,4 xylenol when investigated in guinea pigs in the Maximisation test.
Executive summary:

In a dermal sensitization study, guinea pigs (20/sex) received intradermal injections of 0.5% 2,4 xylenol (administered in Lutrol E 400 DAB and Freund’s Complete Adjuvant (FCA)) / 0.9% NaCl (1:1)). The treatment regime involved induction of sensitization by intradermal injection on day 1, induction of sensitization by topical administration one week later (25% 2,4 xylenol in Lutrol E 400 DAB), challenge by topical administration on day 21 (5% 2,4 xylenol in Lutrol E 400 DAB), followed by a rechallenge on day 28 (5% 2,4 xylenol in Lutrol E 400 DAB).

Following intradermal induction, 0.5% 2,4 xylenol caused swelling and moderate erythema. One week laterm percutaneous induction with 25% 2,4 xylenol in Lutrol E 400 DAB resulted in swelling and necrotic changes. Following challenge, 11/20 test animals test animals showed a positive allergic reaction. Following rechallenge 8/20 test animals showed a positive allergic reaction. The 5% 2,4 xylenol applied to control animals was tolerated and no skin reactions were observed in the control groups.

2,4 xylenol showed a clear skin sensitisation potential in this study.